Statins For Primary Prevention Research Articles

Association of lipid target achievement and cardiovascular outcomes following statin initiation: a population-based cohort study

Abstract Introduction Non-high density lipoprotein cholesterol (non-HDL-C) is increasingly incorporated into clinical practice guidelines along with low density lipoprotein cholesterol (LDL-C) to guide lipid-lowering therapy decisions. We aimed to examine patterns of LDL-C and non-HDL-C levels after statin initiation for primary prevention of cardiovascular disease (CVD), and their association with incident CV events. Methods We conducted a population-based cohort study of Ontario, Canada residents age ≥66 years who initiated a statin for primary prevention between January 1, 2012 and December 31, 2019. For those surviving 1-year after statin initiation, we determined the proportion with a lipid panel in the 1-year period after a statin was started. For those with a lipid panel, we used the lipid panel closest to the end of the 1-year period to categorize individuals based on the LDL-C and non-HDL-C thresholds in the 2021 Canadian Cardiovascular Society dyslipidemia guidelines (Table 1). We stratified by diabetes/chronic kidney disease (CKD) status. We evaluated the association between LDL-C/non-HDL-C category and a composite of all-cause mortality or hospitalization for myocardial infarction, stroke or revascularization (primary outcome). We also investigated the association between each category and each component of the primary outcome. The index date was the 365 days after a statin was initiated and follow-up was until December 31, 2020. We used a cause-specific hazards model for analysis, adjusted for clinical and sociodemographic confounders. Results Our cohort comprised 173,127 people. In the 1-year period after statin initiation, 72% of people had a follow-up lipid panel performed. Median follow-up after that was 2.5 years. Compared with those meeting both LDL-C and non-HDL-C targets, being above both targets was associated with an increased rate of the primary outcome for people without diabetes/CKD (HR 1.10, 95% CI 1.05 to 1.15) and those with diabetes/CKD (HR 1.16, 95% CI 1.09 to 1.23). Being at LDL-C target but above non-HDL-C target was associated with an increased rate of the primary outcome for people with diabetes/CKD (HR 1.16, 95% CI 1.03 to 1.30) but not for those without diabetes/CKD (HR 1.05, 95% CI 0.93 to 1.17). Conclusions In this population-based cohort, having an LDL-C and non-HDL-C above guideline-recommended targets after statin initiation was associated with an increased rate of adverse outcomes. These findings support the residual risk associated with incompletely controlled LDL-C or non-HDL-C levels after initiating statin therapy for primary prevention.Primary outcome associationsComponents of primary outcome

Artificial intelligence-enhanced electrocardiography predicts 10-year risk of atherosclerotic cardiovascular disease

Abstract Background The ACC/AHA pooled cohort equations (PCE) calculates the 10-year primary risk of atherosclerotic cardiovascular disease (ASCVD), an indication to initiate primary prevention statin therapy in international guidelines. The validity of PCE is limited by its overestimation of risk in high-risk cohorts and an ethnic heterogeneity. Electrocardiography (ECG) has not been incorporated in current ASCVD risk estimation tools. Artificial Intelligence (AI)-based models are capable to capture patterns that are informative for cardiovascular prognosis. Purpose We explored the predictive value of a discrete-time survival model in 10-year ASCVD risk in comparison to PCE. Methods We developed an AI-ECG model to predict the 10-year ASCVD risk in an unselected secondary care population from the USA comprised of 1,163,401 ECGs from 189,539 patients. Data was split into training/validation and hold-out test sets by patient ID. Our AI-ECG model uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves, accounting for both time to event and censorship (i.e., loss to follow up). We compared the performance of out AI-ECG model using a subset of outpatient data (n=4590) of the BIDMC dataset to PCE and ASCVD risk factors including systolic blood pressure, total cholesterol, HDL cholesterol, hypertension, smoking history, diabetes mellitus, and ethnicity. Performances were evaluated using cox survival analysis. Our AI-ECG model was externally validated in the UKB Biobank (UKB), where we compared the performance of our AI-ECG model to predictions of existing AI-ECG models such as the Stanford Estimator of Electrocardiogram Risk (SEER) model. Results Our AI-ECG successfully predicted future ASCVD events in individuals (C-index 0.721 (0.719-0.723), 5-year AUC 0.761 (0.758-0.763), and differentiated between high and low risk group with an adjusted HR of 2.33 (2.26-2.41). Upon internal validation our AI-ECG model showed a superior performance (C-index 0.679 (0.651-0.708)) than PCE (0.605 (0.577-0.634)) and all risk factors combined (C index 0.642 (0.613-0.672)). When combining AI-ECG predictions with all risk factors, the model showed additional predictive value (0.686 (0.657-0.715)) (Figure 1). Our AI-ECG model showed modest predictive value within the UKB dataset (C-index 0.655 (0.637-0.673)), but significantly outperformed the SEER model (C-index 0.547 (0.527-0.567), p <0.0001 for comparison with AIRE). Conclusion We have shown the potential of AI-ECG models in predicting future ASCVD risks. AI-ECG models demonstrated accurate discrete time survival prediction and good classification performance superior to that of the SEER model, as well as PCE and ASCVD risk factors. . Accurate risk assessment of ASCVD may help prevent adverse events in high risk subjects and save unnecessary pharmacological interventios in low risk subjects.Figure 1

Rationale for Increasing Doses of Statins in Everyday Clinical Practice

HMG-CoA reductase inhibitors (statins) were discovered in the early 1970s in Japan and were originally used to treat patients with hereditary hyperlipidemia. In the late 1990s and early 2000s, clinical trials using statins for primary and secondary prevention showed the possibility of reducing cardiovascular (CV) and, in some cases, all-cause mortality. Intensive statin therapy (atorvastatin 80 mg/day and rosuvastatin 40 mg/day) compared to initial doses provides an additional 16% reduction in CV complications. Regression studies with the original rosuvastatin using intracoronary ultrasound and other modern methods have shown the possibility of stabilization and regression of atherosclerosis in the carotid and coronary arteries. High-dose statin therapy is generally well tolerated; the incidence of clinically significant adverse liver reactions does not exceed 2-3 per 100,000 people, and the incidence of myopathies with increased creatine kinase over 10 upper limits of normal is not higher than 1 per 10,000 people per year. Long-term statin treatment does not increase the risk of dementia and, in some studies, reduced the risk of Alzheimer's disease. Achieving target levels of low-density lipoprotein cholesterol (LDL-C) in routine practice does not exceed 5-11%; one of the main reasons for that is the rare (2-3%) prescription of high doses of statins. Increasing statin doses in routine clinical practice will optimize the treatment of patients with high CV risk and will contribute to further reduction of mortality in our country.

Statins during Anticoagulation for Emergency Life-Threatening Venous Thromboembolism: A Review.

Venous thromboembolism (VTE) is the leading cause of morbidity and death worldwide, after cancer and cardiovascular diseases. VTE is defined to include pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Approximately 25% of PE patients experience sudden death as an initial symptom of VTE, and between 10% and 30% of patients die within the first month after diagnosis. Currently, the only drugs approved for the treatment of both acute and chronic VTE are vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). However, their effectiveness is limited due to their associated risk of bleeding. Ideally, therapy should be able to treat VTE and limit the risk of VTE recurrence without increasing the risk of bleeding. Several studies have shown that the use of statins during anticoagulation for VTE reduces the risk of death and VTE recurrence. However, to date, there are conflicting data on the impact of statins during anticoagulation for VTE. A biological protective function of statins during anticoagulation has also been reported. Statins affect D-dimer levels; tissue factor (TF) gene expression; and VIII, VII, and Von Willebrand clotting factors-the major clotting factors they are able to affect. However, the usefulness of statins for the treatment and prevention of VTE is currently under debate, and they should not be substituted for guideline-recommended VTE prophylaxis or anticoagulation treatment. In this review of the literature, we illustrate the advances on this topic, including data on the role of statins in primary VTE prevention and secondary VTE prevention, related biological mechanisms, the risk of bleeding during their use, and their ability to reduce the risk of death.

Statins for Primary Prevention of Cardiovascular Disease—With PREVENT, What’s a Clinician to Do?

This Viewpoint explores decision thresholds and the evidence that informs them as well as how clinicians may respond to an updated risk estimation model, such as the Predicting Risk of cardiovascular disease EVENTs equations.

Prescription patterns of statins in cirrhotic patients: a survey among primary care physicians and cardiologists

Background Statin therapy is widely utilized for preventing atherosclerotic cardiovascular disease, both as a primary and secondary measure. Despite the American Association for the Study of Liver Diseases’ endorsement of statin use in cirrhotic patients, practitioners exhibit hesitancy, primarily due to concerns regarding hepatotoxicity. This study aimed to evaluate statin prescription patterns in cirrhotic patients by primary care physicians (PCPs) and cardiologists through a survey. Methods A voluntary survey via Survey Monkey with nine objective-type questions was sent to 220 PCPs and 75 cardiologists within Allegheny Health Network. Survey results were collected, and a chi square test was used to compare the two groups. A P value ≤ 0.05 was considered statistically significant. Results A total of 64 PCPs (29.1%) and 15 cardiologists (20%) completed the survey. Overall, 12.6% did not prescribe statins for primary prevention of atherosclerotic cardiovascular disease in compensated cirrhotic patients. While all cardiologists prescribed statins for secondary prevention, over 50% preferred lower-intensity options. Conversely, 14.1% of PCPs avoided statin prescriptions for secondary prevention. Cardiologists were significantly more inclined to prescribe statins, especially for cirrhosis due to metabolic dysfunction-associated steatotic liver disease compared to PCPs (73.3% vs 45.3%, P = 0.05). Conclusions Despite increasing evidence favoring use of statins in cirrhosis for improving portal hemodynamics and decreasing ascites, hepatic encephalopathy, the incidence of hepatocellular carcinoma, and mortality, there is still hesitation on the part of prescribers for the fear of worsening liver disease. Wider dissemination of current guidelines and education practices may help to bridge this gap.

Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations

In 2023, the American Heart Association (AHA) developed the Predicting Risk of Cardiovascular Disease Events (PREVENT) equations to estimate 10-year risk of atherosclerotic cardiovascular disease (ASCVD), as an update to the 2013 pooled cohort equations (PCEs). The PREVENT equations were derived from contemporary cohorts and removed race and added variables for kidney function and statin use. To compare national estimates of 10-year ASCVD risk using the PCEs and PREVENT equations and how these equations affect recommendations for primary prevention statin therapy. This cross-sectional study included adults aged 40 to 75 years who participated in the National Health and Nutrition Examination Survey from 2017 to March 2020. Adults were defined as eligible for primary prevention statin use based on the 2019 AHA/American College of Cardiology guideline on the primary prevention of cardiovascular disease. Data were weighted to be nationally representative and were analyzed from December 27, 2023, to January 31, 2024. The 10-year ASCVD risk and eligibility for primary prevention statin therapy based on PREVENT and PCE calculations. In the weighted sample of 3785 US adults (mean [SD] age, 55.7 [9.7] years; 52.5% women) without known ASCVD, 20.7% reported current statin use. The mean estimated 10-year ASCVD risk was 8.0% (95% CI, 7.6%-8.4%) using the PCEs and 4.3% (95% CI, 4.1%-4.5%) using the PREVENT equations. Across all age, sex, and racial subgroups, compared with the PCEs, the mean estimated 10-year ASCVD risk was lower using the PREVENT equations, with the largest difference for Black adults (10.9% [95% CI, 10.1%-11.7%] vs 5.1% [95% CI 4.7%-5.4%]) and individuals aged 70 to 75 years (22.8% [95% CI, 21.6%-24.1%] vs 10.2% [95% CI, 9.6%-10.8%]). The use of the PREVENT equations instead of the PCEs could reduce the number of adults meeting criteria for primary prevention statin therapy from 45.4 million (95% CI, 40.3 million-50.4 million) to 28.3 million (95% CI, 25.2 million-31.4 million). In other words, 17.3 million (95% CI, 14.8 million-19.7 million) adults recommended statins based on the PCEs would no longer be recommended statins based on PREVENT equations, including 4.1 million (95% CI, 2.8 million-5.5 million) adults currently taking statins. Based on the PREVENT equations, 44.1% (95% CI, 38.6%-49.5%) of adults eligible for primary prevention statin therapy reported currently taking statins, equating to 15.8 million (95% CI, 13.4 million-18.2 million) individuals eligible for primary prevention statins who reported not taking statins. This cross-sectional study found that use of the PREVENT equations was associated with fewer US adults being eligible for primary prevention statin therapy; however, the majority of adults eligible for receiving such therapy based on PREVENT equations did not report statin use.

Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults : Real-World Evidence From a Target Trial Emulation Study.

There is little consensus on using statins for primary prevention of cardiovascular diseases (CVDs) and all-cause mortality in adults aged 75 years or older due to the underrepresentation of this population in randomized controlled trials. To investigate the benefits and risks of using statins for primary prevention in old (aged 75 to 84 years) and very old (aged ≥85 years) adults. Sequential target trial emulation comparing matched cohorts initiating versus not initiating statin therapy. Territory-wide public electronic medical records in Hong Kong. Persons aged 75 years or older who met indications for statin initiation from January 2008 to December 2015 were included. Participants with preexisting diagnosed CVDs at baseline, such as coronary heart disease (CHD), were excluded from the analysis. Among 69 981 eligible persons aged 75 to 84 years and 14 555 persons aged 85 years or older, 41 884 and 9457 had history of CHD equivalents (for example, diabetes) in the respective age groups. Initiation of statin therapy. Incidence of major CVDs (stroke, myocardial infarction, or heart failure), all-cause mortality, and major adverse events (myopathies and liver dysfunction). Of 42 680 matched person-trials aged 75 to 84 years and 5390 matched person-trials aged 85 years or older (average follow-up, 5.3 years), 9676 and 1600 of them developed CVDs in each age group, respectively. Risk reduction for overall CVD incidence was found for initiating statin therapy in adults aged 75 to 84 years (5-year standardized risk reduction, 1.20% [95% CI, 0.57% to 1.82%] in the intention-to-treat [ITT] analysis; 5.00% [CI, 1.11% to 8.89%] in the per protocol [PP] analysis) and in those aged 85 years or older (ITT: 4.44% [CI, 1.40% to 7.48%]; PP: 12.50% [CI, 4.33% to 20.66%]). No significantly increased risks for myopathies and liver dysfunction were found in both age groups. Unmeasured confounders, such as lifestyle factors of diet and physical activity, may exist. Reduction for CVDs after statin therapy were seen in patients aged 75 years or older without increasing risks for severe adverse effects. Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older. Health Bureau, the Government of Hong Kong Special Administrative Region, China, and National Natural Science Foundation of China.

Stage IV non-small cell lung cancer in Veterans undergoing lung cancer screening who were not prescribed statins despite U.S. Preventative Services Task Force recommendations.

e20583 Background: It is well established that Veterans eligible for lung cancer screening (LCS) are also at risk of atherosclerotic cardiovascular disease (ASCVD) due to smoking. Current concepts suggest that statins could play a role in lung cancer prevention and treatment. Accordingly, the purpose of this retrospective, quality improvement project was to determine whether newly diagnosed stage IV non-small cell lung cancer (NCSLC) rate is higher in Veterans undergoing LCS who were not prescribed statins despite U.S. Preventative Services Task Force (USPSTF) recommendations. Methods: Electronic health records of Veterans undergoing LCS and subsequently diagnosed with NSCLC at the Jesse Brown VA Medical Center, Chicago, Illinois between 2021 and 2023 were reviewed. In each case, pertinent demographic, clinical, pathological, and pharmacy data were retrieved. The American College of Cardiology’s ASCVD Risk Estimator was used to assess the Veteran’s 10-year risk for a first ASCVD event. Data are presented as means ± SD. Statistical analysis was performed using Student’s t- and chi-squared tests as indicated. P < 0.05 was considered statistically significant. Results: Out of 57 Veterans diagnosed NSCLC, 33 (all males; 71±6 years; 28 African Americans) were prescribed and 24 (21 males, 3 females; 70±7 years; 18 African Americans) were not prescribed statins. Body mass index was similar in both groups (26.6±6.0 and 26.0±6.0 kg/m2, respectively; p = 0.73). Twenty one out of 24 Veterans (88%) not prescribed statins were eligible according to USPSTF recommendations (10-year calculated risk, 15.23%±6.9%). Stage IV NSCLC was diagnosed in 7/33 (21%) Veterans prescribed statins and in 10/21 (48%) USPSTF-eligible Veterans not prescribed statins (p < 0.05). Conclusions: Clinicians should assess the needfor a statin for primary prevention of ASCVD in each Veteran undergoing LCS. Stage IV NSCLC is more prevalent in Veterans with ASCVD risk who were not prescribed statins despite USPSTF recommendations. A larger, multi-site study is warranted to support or refute these initial observations.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults

BackgroundStatins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). ObjectiveInvestigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. MethodsWe included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and ‘moderate or high’ intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. ResultsCompared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17–1.95); p<0.01], stroke [HR 1.47 (1.14–1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19–1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. ConclusionLack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Low-Intensity Statin Plus Ezetimibe Versus Moderate-Intensity Statin for Primary Prevention: A Population-Based Retrospective Cohort Study in Asian Population.

While moderate-intensity statin therapy is recommended for primary prevention, statins may not be utilized at a recommended intensity due to dose-dependent adverse events, especially in an Asian population. However, evidence supporting the use of low-intensity statins in primary prevention is limited. We sought to compare clinical outcomes between a low-intensity statin plus ezetimibe and a moderate-intensity statin for primary prevention. This population-based retrospective cohort study used the Korean nationwide claims database (2002-2019). We included adults without atherosclerotic cardiovascular diseases who received moderate-intensity statins or low-intensity statins plus ezetimibe. The primary outcome was a composite of all-cause mortality, myocardial infarction, and ischemic stroke. The safety outcomes were liver and muscle injuries and new-onset diabetes mellitus (DM). We used standardized inverse probability of treatment weighting (sIPTW) and propensity score matching (PSM). In the sIPTW model, 1717 and 36 683 patients used a low-intensity statin plus ezetimibe and a moderate-intensity statin, respectively. In the PSM model, each group included 1687 patients. Compared with moderate-intensity statin use, low-intensity statin plus ezetimibe use showed similar risks of the primary outcome (hazard ratio [HR] = 0.92, 95% CI = 0.81-1.12 in sIPTW and HR = 1.16, 95% CI = 0.87-1.56 in PSM model). Low-intensity statin plus ezetimibe use was associated with decreased risks of liver and muscle injuries (subHR [sHR] = 0.84, 95% CI = 0.74-0.96 and sHR = 0.87, 95% CI = 0.77-0.97 in sIPTW; sHR = 0.84, 95% CI = 0.72, 0.96 and sHR = 0.82, 95% CI = 0.72-0.94 in PSM model, respectively). For new-onset DM and hospitalization of liver and muscle injuries, no difference was observed. Low-intensity statin plus ezetimibe may be an alternative to moderate-intensity statin for primary prevention. Our findings provide evidence on safety and efficacy of statin therapy in Asian population.

Abstract P510: Trends in Statin Therapy for Primary Prevention Among Older Veterans, 2003-2020

Introduction: The burden and risk of atherosclerotic cardiovascular disease (ASCVD) in US Veterans is higher than the general population, yet rates of use of medications for primary prevention, specifically statins, are not well described. Since the early 2000s, trial data have proven the efficacy of statins for primary prevention, further encouraged by updated guidelines (notably 2001, 2013, 2018). Therefore, we sought to examine the proportion of older veterans free of ASCVD and trends of statin use for primary prevention within this cohort from 2003 to 2020. Methods: Study participants comprised all US Veterans ≥65 years, free of ASCVD, and with at least one visit in the Veteran’s Health Administration (VHA) in the year prior. Statin users had at least two or more prescriptions of any statin in each one-year period studied. VA prescription data were linked to Medicare/Medicaid to ensure complete capture of statin use. Descriptive statistics and crude proportions were calculated by year of study entry. Results: From 2003-2020, there were 5.1 million Veterans aged 65 and older who received regular care in VHA. The overall proportion of veterans free of ASCVD in that period was 60% (N=3,159,705). Statin prescriptions for primary prevention have increased from 39% in 2003 to 52% in 2020, remaining steady after 2007. For example, in 2011, 51% were prescribed statins, mean age 73±7, 87% white, 98% male, 82% hypertension, 37% diabetes, 94% hyperlipidemia; while in 2017, 53% were prescribed statins (age 72± 7, 80% white, 97% male, 73% hypertension, 31% diabetes, 74% hyperlipidemia), received statin therapy for primary prevention (Figure). Conclusion: A substantial proportion of Veterans ≥65 years were at risk for ASCVD. While statin prescriptions for primary prevention have increased from 2003-2020, over the past 15 years, they have remained at around 50%. These findings indicate a focus on primary prevention among older Veterans is needed.

Effect of Statins for Primary Prevention of Cardiovascular Disease According to the Fatty Liver Index

IntroductionNonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD.MethodsWe conducted a nested case–control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed.ResultsWithin a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case–control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20–1.40, P < 0.001]. In sub-analyses based on FLI tertiles, statin therapy was associated with a lower risk of CVD (adjusted OR 0.72; 95% CI 0.61–0.85, P < 0.001) in the T3 tertile but not in the T1 and T2 tertiles.ConclusionsStatin therapy was associated with a reduced risk of CVD in individuals with high FLI but not in those with low FLI. Further research is needed to determine the pathophysiologic mechanism between statin and NAFLD.

Effect of statin use for the primary prevention of cardiovascular disease among older adults: a cautionary tale concerning target trials emulation

ObjectivesEvidence concerning the effect of statins in primary prevention of cardiovascular disease (CVD) among older adults is lacking. Using Quebec population-wide administrative data, we emulated a hypothetical randomized trial including older adults >65 years on April 1, 2013, with no CVD history and no statin use in the previous year. Study Design and SettingWe included individuals who initiated statins and classified them as exposed if they were using statin at least 3 months after initiation and nonexposed otherwise. We followed them until March 31, 2018. The primary outcome was the composite endpoint of coronary events (myocardial infarction, coronary bypass, and percutaneous coronary intervention), stroke, and all-cause mortality. The intention-to-treat (ITT) effect was estimated with adjusted Cox models and per-protocol effect with inverse probability of censoring weighting. ResultsA total of 65,096 individuals were included (mean age = 71.0 ± 5.5, female = 55.0%) and 93.7% were exposed. Whereas we observed a reduction in the composite outcome (ITT–hazard ratio (HR) = 0.75; 95% CI: 0.68–0.83) and mortality (ITT-HR = 0.69; 95% CI: 0.61–0.77) among exposed, coronary events increased (ITT-HR = 1.46; 95% CI: 1.09–1.94). All multibias E-values were low indicating that the results were not robust to unmeasured confounding, selection, and misclassification biases simultaneously. ConclusionWe cannot conclude on the effectiveness of statins in primary prevention of CVD among older adults. We caution that an in-depth reflection on sources of biases and careful interpretation of results are always required in observational studies.

Older Adult Attitudes toward Deprescribing Statins in Primary Cardiovascular Prevention Versus General Medications.

Background: There is little evidence for statins for primary cardiovascular prevention in older adults. Consequently, it is important to assess patient attitudes toward the use of statins, which might differ from attitudes toward other medications. We aimed to describe older patient attitudes toward deprescribing statins versus general medications. Methods: We conducted a survey using the revised Patients' Attitudes Toward Deprescribing questionnaire in its original version and adapted to statin use in adults ≥65 years taking a statin for primary prevention. Results: Among the 47 participants (mean age 74.6 years), 42 (89%) were satisfied with their current therapy, but still willing to stop ≥1 of their medications upon their doctor's advice. About 68% (N = 32) were satisfied with their statin therapy, while 83% (N = 39) would accept to consider deprescribing. Twenty-six (55%) participants were concerned about missing future benefits when stopping their general medications and 17 (36%) when stopping their statin. Eight (17%) participants believed they were experiencing side effects of statins and twice as many for general medication (38%, N = 18). Conclusion: Our study provides insight about differences and similarities in patient attitudes toward deprescribing general medications and statins in primary prevention. This information could support patient-centered conversations and shared-decision making about deprescribing.

Older Adult Perspectives on Statin Continuation and Discontinuation in Primary Cardiovascular Disease Prevention: A Mixed-Methods Study.

Evidence for statin use for primary cardiovascular disease prevention in older adults is limited. When evidence on risk-benefit profile of a medication is uncertain, using it or not becomes a preference-sensitive decision. We aimed to assess and explore patient perspectives on continuation and discontinuation of statins used for primary cardiovascular prevention in older adults. We used a convergent mixed-methods design, conducting in parallel a survey among 47 patients and three focus groups (FGs) with 14 patients total. We recruited patients aged ≥65 years and taking a statin for primary cardiovascular prevention. The survey and FGs aimed to assess and explore patient experiences of statin use, and views on statin continuation and discontinuation, including patient decision-making. Quantitative and qualitative data were first analyzed separately - descriptive statistics for quantitative data and thematic analysis for qualitative data - and then integrated to create metainferences, using joint displays. Forty-one percent of patients (N=19) were reluctant to discontinue the statin, whereas 22% (N=10) were willing to try discontinuing it. A reason to continue the statin was its perceived necessity, while self-estimated low cardiovascular risk and wish to reduce medication burden were given as reasons to discontinue it. Lack of expertise assumed by the patients to decide about statin continuation or discontinuation, uncertainty about statin indication, and fear of having a cardiovascular event after discontinuation made many patients uncertain about deciding to continue or discontinue the statin. In this context, 70% (N=33) would rather have their physician choose for them, and 94% (N=44) would continue taking the statin for as long as their physician told them to do so. This study highlights factors that influence patient willingness to continue or discontinue statins, patient uncertainty about statin continuation or discontinuation, and the important role physicians play in the decision-making process.

Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease

There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD). To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4. This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023. Statin initiation vs none. Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality). Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses. In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.

Decision curve analysis based on summary data.

To realize the potential of precision medicine, predictive models should be integrated within the framework of decision analysis, such as the decision curve analysis (DCA). To date, its application has required individual patient data (IPD) that are often unavailable. Performing DCA using aggregate data without requiring IPD may advance the goals of precision medicine. We present a statistical framework demonstrating that DCA can be conducted by using only the mean and standard deviation (SD) from the raw probabilities of the predictive model. We tested our theoretical framework by performing extensive simulations and comparing the aggregate-based DCA with IPD DCA. The latter was conducted using IPD from four predictive models that employed logistic regression, Coxor competing risk time-to-event modeling including(a) statins for primary prevention of cardiovascular disease (n = 4859), (b) hospice referral for terminally ill patients (n = 9104), (c) use of thromboprophylaxis for preventing venous thromboembolismin patients with cancer (n = 425)and (d) prevention of sinusoidal obstruction syndromeafter hematopoietic cell transplantation (SCT) (n = 80). Simulations assuming perfect calibration showed that regardless of which probability distributions informed the predictive models, the differences in DCA were negligible. Similarly, for the adequately powered models, the results of DCA based on the summary data were similar to IPD-derived DCA. The inherent instability of the predictive models, based on the smaller sample sizes, resulted in a somewhat larger discrepancy between aggregate and IPD-based DCA. DCA informed by adequately powered and well-calibrated models using only summary statistical estimates (mean and SD) approximates well models using IPD. Use of aggregate data will facilitate broader integration of predictive with decision modeling toward the goals of individualized decision-making.

Identification of subgroups within a Japanese older adult population for whom statin therapy is effective in reducing mortality.

Use of statins for primary prevention can reduce all-cause mortality in Asian elderly populations, but their effect and the specific effective subgroups in the elderly Japanese population remain unclear. This study examined the relationship between statin therapy for primary prevention and mortality reduction in older Japanese adults, and investigated the effective subgroups. The cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33-0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group compared with that in the control group was 0.05 (95% CI, 0.04-0.06), and the number needed to treat was 21.20 (95% CI, 18.10-24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to <85 years and in patients with comorbidities such as diabetes, or dementia.

An audit of a general practices compliance with national recommendations for the avoidance of complications for type 2 diabetic patients

Abstract Introduction Each week, diabetes leads to more than 700 strokes, almost 600 heart attacks and more than 2000 instances of heart failure, in addition to being the single most common cause of chronic kidney disease in the UK.1 The NHS spends 10% of its annual budget on diabetes with 80% of that treating the complications of diabetes.2 Pharmacists have a crucial role to optimise the medication of diabetic patients and prevent future problems. Aim To assess a general practices (GP) compliance with national recommendations and the Quality and Outcomes Framework for the avoidance of complications for Type 2 Diabetes Mellitus (T2DM) patients. Methods This single-centre, retrospective audit was conducted at a GP in the London Borough of Southwark. Six standards were measured focusing on the prevention of the complications of diabetes. Each standard incorporated an exclusion and inclusion criteria. Standard 1 and 2 reviewed the appropriate management of nephropathy and hypertension respectively. Standard 3 and 4 relate to statin use for primary and secondary prevention. The final standards assess how many patients have documented QRISK2 scores and initiated on a Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitor as per the new NICE guidelines.3 Ethical approval was not deemed necessary for this clinical audit in agreement with the Hurley Group and King’s College Hospital NHS Foundation Trust guidelines. Results Half (50%, n=153/304) of all included T2DM patients at the practice have a blood pressure reading defined as hypertensive. Out of all diabetic patients, 25 of them had clinical proteinuria, micro-albuminuria, or a diagnosis of nephropathy. Of these 25 patients, 19 (76%) were prescribed an angiotensin-converting enzyme inhibitor or angiotensin-receptor blockers. A small portion (7%, n=28/374) of the diagnosed T2DM patients have a documented QRISK2 score. Subsequently, only 32 diabetic patients (9%, n=32/374) are prescribed an SGLT2 inhibitor. For standards 3 and 4, there were 122 patients (73%) who were prescribed a statin for primary prevention and 89 patients (87%) who were prescribed a statin for secondary prevention. Discussion/Conclusion The microvascular and macrovascular complications of diabetes are well documented. The incidence of these complications can be reduced by pharmacological management. Although none of the standards were met, the results are similar to other practices across the country. However, in comparison to the local average, the audited GP underperformed with no standards being better than the average of GPs in the area. Sub-analysis emphasises the disparities in health between various racial and ethnic groups. The results of the two largest demographic groups audited, Caucasian and Caribbean patients, show that the former is more likely to meet the standards. These findings indicate that the processes of the practice require change to meet the needs of our diabetic patients. In particular, work is required to understand the disparities in care for our patients categorised as ethnic minorities. The recommendations fall under 5 main categories – feedback, learn, templates, analyse, and review.